MTHFD1 p.Lys71=
c.213G>A · VCV4772037
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 3.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
South Asian · 21/91,074 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.0013%
21/1,613,780 alleles · ultra-rare
exomes 20/1,461,536 · genomes 1/152,244 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MTHFD1
- Protein
- p.Lys71=
- Coding
- c.213G>A
- MANE Select
- NM_005956
- Type
- single nucleotide variant
- Location
- chr14:64412498 (GRCh38)
- Gene constraint
- LOEUF 0.51 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 94.63 · 12 PDB
- Residue 71
- the 'methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (d/c) domain' region; a β-strand
Similar variants
- MTHFD1 p.Lys71Asn Uncertain significance ★ ⚠ same residue
- MTHFD1 c.727+1G>A Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 p.Arg173Cys Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 p.Gln100Ter Likely pathogenic ★★ same type
- MTHFD1 p.Glu225Ter Pathogenic ★★ same type
- MTHFD1 p.Ser49Phe Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 c.186+5C>T Uncertain significance ★★ same type
- MTHFD1 p.Arg173His Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mthfd1-p-lys71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown